Endothelin and sex hormones modulate the fibronectin synthesis by cultured human skin scleroderma fibroblasts.
OBJECTIVE
To evaluate the influence of endothelin-1 (ET-1) and sex hormones on cell proliferation and extracellular matrix (ECM) synthesis (ie, fibronectin, laminin) by cultured normal and scleroderma (SSc) human skin fibroblasts (FBs).


METHODS
Primary cultures of FBs were treated with ET-1 and sex hormones (17beta-oestradiol or testosterone) for 24 h. Cell growth was analysed by methiltetrazolium salt test, ECM synthesis was evaluated by immunocytochemistry and western blot, both at 24 h.


RESULTS
In normal FBs, ET-1 and 17beta-oestradiol, as well as their combination, increased cell growth (p<0.001, p<0.001, p<0.01 vs untreated cells (control), respectively) and fibronectin synthesis (p<0.05, p<0.05, p<0.01 vs control, respectively). By contrast, testosterone either alone or in combination with ET-1 did not influence cell proliferation, but decreased fibronectin synthesis (p<0.05, testosterone vs control). In SSc FBs, ET-1 and 17beta-oestradiol alone or their combination induced an increased fibronectin synthesis (p<0.05, p<0.05, p<0.01 vs control, respectively). Unexpectedly, testosterone induced an increase of fibronectin synthesis (p<0.05 vs control).


CONCLUSIONS
ET-1 and 17beta-oestradiol seem to exert a profibrotic effect in normal and SSc culture FBs and might suggest their synergistic effect in the pathogenesis of the fibrotic process in SSc.
Soldano
S
S
Research Laboratories and Clinical Academic Unit of Rheumatology, Department of Internal Medicine, University of Genova, Italy.
Montagna
P
P
Villaggio
B
B
Parodi
A
A
Gianotti
G
G
Sulli
A
A
Seriolo
B
B
Secchi
M E
ME
Cutolo
M
M
D015153:Blotting, Western / Q000379:methods; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004357:Drug Synergism; D019332:Endothelin-1 / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000096:biosynthesis*; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D012594:Scleroderma, Localized / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*; D018709:Statistics, Nonparametric; D013739:Testosterone / Q000494:pharmacology
D019332:Endothelin-1; D005353:Fibronectins; D012739:Gonadal Steroid Hormones; D013739:Testosterone; D004958:Estradiol